Natural killer, but not natural killer T, cells play a necessary role in the promotion of an innate antitumor response induced by IL-18.

Abstract

IL-18 administration promotes innate immunity resulting in significant antitumor effects in multiple murine tumor models. Here, we examined the effector population mediating the innate immunity. Most NK cells and some NKT cells express IL-18Rs without prior stimulation (65% positive in NK cells, 18% positive in NKT cells), though few naive T cells do. In vivo depletion of NK cells, but not NKT cells, using AsGM1 antibody significantly reduces IL-18-induced cytotoxicity. However, NK-like activity of hepatic MNCs for the NK target YAC-1 was present in Valpha 14 NKT cell-deficient animals. Furthermore, administration of rIL-18 greatly reduced B16 pulmonary metastases in vivo in NKT cell-deficient animals. When sorted NK and NKT cells were exposed to IL-18 in vitro, NK cells showed more IFN-gamma production and cytolysis against YAC-1 than NKT cells in response to IL-18. These results are consistent with the notion that NK cells, but not NKT cells, are the major effectors in IL-18-induced innate immunity.